Postępowanie zmniejszające ryzyko wystąpienia raków BRCA- zależnych u nosicieli mutacji BRCA1/2 – nowe światło na stare spojrzenie

• Authors: Jarosław Mądry , Anna Markowska

Title variants

EN

Reduction of risk of developing BRCA-dependent cancer in BRCA1/2 mutation carriers – novel approach to old paradigm

• Languages of publication: EN PL

Abstracts

EN

Carriers of mutations in BRCA1 and BRCA2 genes undergo a significantly increased risk of developing breast cancer, ovarian cancer, fallopian tube cancer and peritoneal cancer. Due to genetic homogeneity of Polish population, the key issue are mutations of BRCA1 gene. Mutations of 5382insC, C61G and 4153delA constitute about 90% of all BRCA1 gene mutations. Mean cumulative risk of development of ovarian cancer by carriers of BRCA1 gene mutations under 70 is estimated at 40% and that of breast cancer – at 57%. Management of carriers of BRCA1/2 mutations is multidirectional. Carriers of BRCA1 mutations should be screened for breast cancer. Available data indicate that detection of early forms of ovarian cancer is currently impossible. Use of low-dose oral contraception may reduce the risk of ovarian cancer, while not increasing the risk of breast cancer in BRCA1 mutation carriers. After giving birth to planned/desired number of children, carriers of BRCA1 gene mutation should be offered the option of preventive salpingo-oophorectomy. This may reduce the risk of development of BRCA-dependent tumors to 0.21 (95% CI: 0.12-0.39) and breast cancer to 0.49 (95% CI: 0.37-0.65). Risk reduction for the development of peritoneal cancer is not 100% because some of the patients develop primary peritoneal cancer. The risk of development of this type of tumor is significantly reduced to 0.92% vs. 5.78% in the followed-up group. Upon preventive adnexectomy, these patients may safely benefit from hormonal replacement therapy. Close follow-up is mandatory aiming at an early detection of possible metabolic syndromes. Available model analyzing the impact of several strategies of follow-up and intervention on survival rates of mutation carriers indicates that adnexectomy at the age of 40 is the single most effective intervention in BRCA1 mutation carriers.

PL

Ryzyko zachorowania na raka piersi, jajnika, jajowodu i otrzewnej u nosicieli mutacji w genach BRCA1 i BRCA2 jest istotnie zwiększone. W Polsce, z uwagi na jej genetyczną homogenność, najważniejszą rolę odgrywają mutacje genu BRCA1. Mutacje 5382insC, C61G i 4153delA stanowią 90% wszystkich mutacji genu BRCA1. Średnie skumulowane ryzyko rozwoju raka jajnika u nosicielek mutacji BRCA1 do 70. roku życia wynosiło 40%, a ryzyko raka piersi – 57%. Postępowanie z nosicielami mutacji BRCA1/2 jest postępowaniem wielokierunkowym. Nosiciele mutacji BRCA1 powinni mieć prowadzony skryning raka piersi. Dostępne dane wskazują, że nie ma obecnie możliwości wykrywania wczesnych raków jajnika. Stosowanie niskodawkowej antykoncepcji hormonalnej zmniejsza ryzyko wystąpienia raka jajnika, nie zwiększając w istotny sposób ryzyka raka piersi u nosicieli mutacji BRCA1. Po urodzeniu zaplanowanej liczby dzieci nosicielom mutacji BRCA1 należy proponować profilaktyczne usunięcie jajników i jajowodów (PA). Zabieg ten zmniejsza ryzyko wystąpienia nowotworów BRCA-zależnych do 0,21 (95% CI: 0,12-0,39), a raka piersi – do 0,49 (95% CI: 0,37-0,65). Redukcja ryzyka rozwoju nowotworu w jamie brzusznej nie jest stuprocentowa z uwagi na rozwój u części chorych pierwotnego raka otrzewnej. Ryzyko rozwoju takiego nowotworu jest istotnie mniejsze i wynosi 0,92% w porównaniu z 5,78% w grupie z nadzorem. Po profilaktycznym wycięciu przydatków (PA) pacjentki mogą bezpiecznie otrzymywać HTZ. Konieczny jest również nadzór celem wczesnego wykrywania możliwych zespołów metabolicznych. Dostępny model analizujący wpływ różnych scenariuszy nadzoru i interwencji na czas przeżycia nosicieli mutacji wskazuje, że PA w wieku 40 lat dla nosicieli mutacji BRCA1 jest najbardziej skuteczną pojedynczą interwencją.

Keywords

EN

BRCA1; BRCA2; HTZ; antykoncepcja hormonalna; breast cancer; hormonal contraception; hormonal replacement therapy; ovarian cancer; preventive salpingo-oophorectomy; profilaktyczne usunięcie jajników i jajowodów; rak jajnika; rak piersi

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Current Gynecologic Oncology
• Year: 2010
• Volume: 8
• Issue: 3
• Pages: 188-199

Contributors

author

Jarosław Mądry

• Klinika Onkologii, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu, ul. Łąkowa 1/2, 61-878 Poznań, tel.: [phone], faks: 61 851 04 90, tel. kom.: 501 149 213, Dr n. med., specjalista ginekolog położnik Radosław Mądry. Kierownik Kliniki: prof. dr hab. n. med. Janina Markowska

author

Anna Markowska

• Klinika Perinatologii i Chorób Kobiecych Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu. Kierownik Kliniki: prof. dr hab. n. med. Krzysztof Drews

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• Document Type: article